A Machine Learning Application to Classify Patients at Differing Levels of Risk of Opioid Use Disorder: Clinician-Based Validation Study.

Background: Despite restrictive opioid management guidelines, opioid use disorder (OUD) remains a major public health concern. Machine learning (ML) offers a promising avenue for identifying and alerting clinicians about OUD, thus supporting better clinical decision-making regarding treatment. Objective: This study aimed to assess the clinical validity of an ML application designed to identify and alert clinicians of different levels of OUD risk by comparing it to a structured review of medical records by clinicians. Methods: The ML application generated OUD risk alerts on outpatient data for 649,504 patients from 2 medical centers between 2010 and 2013. A random sample of 60 patients was selected from 3 OUD risk level categories (n=180). An OUD risk classification scheme and standardized data extraction tool were developed to evaluate the validity of the alerts. Clinicians independently conducted a systematic and structured review of medical records and reached a consensus on a patient's OUD risk level, which was then compared to the ML application's risk assignments. Results: A total of 78,587 patients without cancer with at least 1 opioid prescription were identified as follows: not high risk (n=50,405, 64.1%), high risk (n=16,636, 21.2%), and suspected OUD or OUD (n=11,546, 14.7%). The sample of 180 patients was representative of the total population in terms of age, sex, and race. The interrater reliability between the ML application and clinicians had a weighted kappa coefficient of 0.62 (95% CI 0.53-0.71), indicating good agreement. Combining the high risk and suspected OUD or OUD categories and using the review of medical records as a gold standard, the ML application had a corrected sensitivity of 56.6% (95% CI 48.7%-64.5%) and a corrected specificity of 94.2% (95% CI 90.3%-98.1%). The positive and negative predictive values were 93.3% (95% CI 88.2%-96.3%) and 60.0% (95% CI 50.4%-68.9%), respectively. Key themes for disagreements between the ML application and clinician reviews were identified. Conclusions: A systematic comparison was conducted between an ML application and clinicians for identifying OUD risk. The ML application generated clinically valid and useful alerts about patients' different OUD risk levels. ML applications hold promise for identifying patients at differing levels of OUD risk and will likely complement traditional rule-based approaches to generating alerts about opioid safety issues.

Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Outcomes of Arterial Bypass With the Human Acellular Vessel for Chronic Limb-Threatening Ischemia Performed Under the FDA Expanded Access Program.

OBJECTIVE: To report outcomes of the human acellular vessel (HAV) implanted for limb salvage through the Food and Drug Administration (FDA) Expanded Access Program for patients with chronic limb-threatening ischemia with no autologous conduit. METHODS: The HAV is a bioengineered vascular conduit designed with human vascular smooth muscle cells. The product is under regulatory study. From April 2019 to November 2021, the HAV was implanted in 14 patients (12 men; mean age, 62±14 years) at 3 US centers. Each case was performed with a single-use investigational new drug Expanded Access Program issued by the FDA. Institutional review board approval was obtained; technical and clinical outcomes were analyzed. RESULTS: A single 6-mm-diameter (40-cm-long) HAV was implanted in 9 patients; 5 patients required 2 HAVs sewn together as a composite. Technical success was 100%. Median follow-up was 12 (range, 1 to 41) months. Primary and secondary patency rates were 72% and 81% at 12 months; assisted primary patency was attained in 4 patients. Amputation-free survival was 93% at 6 months and 77% at 12 months. All patients with a patent HAV experienced clinical improvement with no HAV-related infections or adverse events. There were 4 deaths in the cohort, late mortality unrelated to the HAV. CONCLUSION: The HAV is a safe and effective "off-the-shelf" biologic conduit. This experience from the FDA Expanded Access Program in this population with few alternative limb salvage options will help guide regulatory deliberations for patients with lower extremity ischemia and no autologous bypass conduit options.

A theoretical study of H2 O2 as the surrogate of dose in minibeam radiotherapy, with a diffusion model considering radical removal process.

BACKGROUND: Minibeam radiation therapy (MBRT) is an innovative dose delivery method with the potential to spare normal tissue while achieving similar tumor control as conventional radiotherapy. However, it is difficult to use a single dose parameter, such as mean dose, to compare different patterns of MBRT due to the spatially fractionated radiation. Also, the mechanism leading to the biological effects is still unknown. PURPOSE: This study aims to demonstrate that the hydrogen peroxide (H2 O2 ) distribution could serve as a surrogate of dose distribution when comparing different patterns of MBRT. METHODS: A free diffusion model (FDM) for H2 O2 developed with Fick's second law was compared with a previously published model based on Monte Carlo & convolution method. Since cells form separate compartments that can eliminate H2 O2 radicals diffusing inside the cell, a term describing the elimination was introduced into the equation. The FDM and the diffusion model considering removal (DMCR) were compared by simulating various dose rate irradiation schemes and uniform irradiation. Finally, the DMCR was compared with previous microbeam and minibeam animal experiments. RESULTS: Compared with a previous Monte Carlo & Convolution method, this analytical method provides more accurate results. Furthermore, the new model shows H2 O2 concentration distribution instead of the time to achieve a certain H2 O2 uniformity. The comparison between FDM and DMCR showed that H2 O2 distribution from FDM varied with dose rate irradiation, while DMCR had consistent results. For uniform irradiation, FDM resulted in a Gaussian distribution, while the H2 O2 distribution from DMCR was close to the dose distribution. The animal studies' evaluation showed a correlation between the H2 O2 concentration in the valley region and treatment outcomes. CONCLUSION: DMCR is a more realistic model for H2 O2 simulation than the FDM. In addition, the H2 O2 distribution can be a good surrogate of dose distribution when the minibeam effect could be observed.

Developing, pilot testing, and refining requirements for 3 EHR-integrated interventions to improve diagnostic safety in acute care: a user-centered approach.

Objective: To describe a user-centered approach to develop, pilot test, and refine requirements for 3 electronic health record (EHR)-integrated interventions that target key diagnostic process failures in hospitalized patients. Materials and Methods: Three interventions were prioritized for development: a Diagnostic Safety Column (DSC) within an EHR-integrated dashboard to identify at-risk patients; a Diagnostic Time-Out (DTO) for clinicians to reassess the working diagnosis; and a Patient Diagnosis Questionnaire (PDQ) to gather patient concerns about the diagnostic process. Initial requirements were refined from analysis of test cases with elevated risk predicted by DSC logic compared to risk perceived by a clinician working group; DTO testing sessions with clinicians; PDQ responses from patients; and focus groups with clinicians and patient advisors using storyboarding to model the integrated interventions. Mixed methods analysis of participant responses was used to identify final requirements and potential implementation barriers. Results: Final requirements from analysis of 10 test cases predicted by the DSC, 18 clinician DTO participants, and 39 PDQ responses included the following: DSC configurable parameters (variables, weights) to adjust baseline risk estimates in real-time based on new clinical data collected during hospitalization; more concise DTO wording and flexibility for clinicians to conduct the DTO with or without the patient present; and integration of PDQ responses into the DSC to ensure closed-looped communication with clinicians. Analysis of focus groups confirmed that tight integration of the interventions with the EHR would be necessary to prompt clinicians to reconsider the working diagnosis in cases with elevated diagnostic error (DE) risk or uncertainty. Potential implementation barriers included alert fatigue and distrust of the risk algorithm (DSC); time constraints, redundancies, and concerns about disclosing uncertainty to patients (DTO); and patient disagreement with the care team's diagnosis (PDQ). Discussion: A user-centered approach led to evolution of requirements for 3 interventions targeting key diagnostic process failures in hospitalized patients at risk for DE. Conclusions: We identify challenges and offer lessons from our user-centered design process.

Radio-resistance of hypoxic tumors: exploring the effects of oxygen and x-ray radiation on non-small lung cancer cell lines.

BACKGROUND: Solid tumors are often riddled with hypoxic areas, which develops as a result of high proliferation. Cancer cells willingly adapt and thrive in hypoxia by activating complex changes which contributes to survival and enhanced resistance to treatments, such as photon radiation. Photon radiation primarily relies on oxygen for the production of reactive oxygen species to induce DNA damage. The present in-vitro study aimed at investigating the biochemical responses of hypoxic non-small cell lung cancer (NSCLC) cells, particularly the effects on the DNA damage repair systems contributing to more radioresistant phenotypes and their pro- and anti-oxidant potential, within the first 24 h post-IR. METHODS: NSCLC cell lines (H460, A549, Calu-1) were irradiated using varying X-ray doses under normoxia (21% O2) and hypoxia (0.1% O2). The overall cell survival was assessed by clonogenic assays. The extent of irradiation (IR)-induced DNA damage was evaluated by analyzing γ-H2AX foci induction and the altered expression of repair genes involved in non-homologous end joining and homologous recombination pathways. Moreover, cell-altered responses were investigated, including the nuclear and cytosolic hydrogen peroxide (H2O2) production, as well as the associated anti-oxidant potential, in particular some components related to the glutathione system. RESULTS: Analysis of clonogenic survival revealed an enhanced radioresistance of the hypoxic NSCLC cells associated with reduced DNA damage and a downregulation of DNA repair genes. Moreover, nuclear H2O2 levels were IR-induced in a dose-dependent manner only under normoxia, and directly correlated with the DNA double-strand breaks. However, the observed nuclear H2O2 reduction in hypoxia appeared to be unaffected by IR, thus highlighting a possible reason for the enhanced radioresistance of the hypoxic NSCLC cells. The cellular antioxidant capacity was upregulated by IR in both oxygen conditions most likely helping to counteract the radiation effect on the cytosolic H2O2. CONCLUSIONS: In conclusion, our data provide insight into the adaptive behavior of radiation-resistant hypoxic NSCLC cells, in particular their DNA repair and oxidative stress responses, which could contribute to lower DNA damage and higher cell survival rates following X-ray exposure. These findings may therefore help to identify potential targets for improving cancer treatment outcomes.

Human Cancer Cell Radiation Response Investigated through Topological Analysis of 2D Cell Networks.

Clonogenic assays are routinely used to evaluate the response of cancer cells to external radiation fields, assess their radioresistance and radiosensitivity, estimate the performance of radiotherapy. However, classic clonogenic tests focus on the number of colonies forming on a substrate upon exposure to ionizing radiation, and disregard other important characteristics of cells such their ability to generate structures with a certain shape. The radioresistance and radiosensitivity of cancer cells may depend less on the number of cells in a colony and more on the way cells interact to form complex networks. In this study, we have examined whether the topology of 2D cancer-cell graphs is influenced by ionizing radiation. We subjected different cancer cell lines, i.e. H4 epithelial neuroglioma cells, H460 lung cancer cells, PC3 bone metastasis of grade IV of prostate cancer and T24 urinary bladder cancer cells, cultured on planar surfaces, to increasing photon radiation levels up to 6 Gy. Fluorescence images of samples were then processed to determine the topological parameters of the cell-graphs developing over time. We found that the larger the dose, the less uniform the distribution of cells on the substrate-evidenced by high values of small-world coefficient (cc), high values of clustering coefficient (cc), and small values of characteristic path length (cpl). For all considered cell lines, [Formula: see text] for doses higher or equal to 4 Gy, while the sensitivity to the dose varied for different cell lines: T24 cells seem more distinctly affected by the radiation, followed by the H4, H460 and PC3 cells. Results of the work reinforce the view that the characteristics of cancer cells and their response to radiotherapy can be determined by examining their collective behavior-encoded in a few topological parameters-as an alternative to classical clonogenic assays.

Diálogos abiertos en un grupo multifamiliar dentro de un programa de atención a primeras crisis psicóticas / Open dialogues in a multifamily group within a program of care for first psychotic crises

Introducción: describimos la experiencia de un grupo multifamiliar, dirigido a jóvenes y su red social, afectados por primeras crisis psicóticas, en la práctica clínica real dentro del Sistema Sanitario Nacional de Salud de España, bajo la filosofía de Diálogos Abiertos, en el contexto de pandemia por COVID-19. Método: Participan 3 familias y 3 profesionales de la red de salud mental. Instrumentos: SCORE-15, SWLS, CSQ-8 y un registro de temas que aparecen en los diálogos. Resultados: tanto los 5 sujetos como las facilitadoras perciben mejoría a nivel de funcionamiento familiar y utilidad de la terapia; solo uno de los sujetos informa de mejoría a nivel de satisfacción vital al finalizar el grupo; observamos una alta satisfacción con la atención recibida en el grupo por parte de los participantes. Discusión: la fortaleza de este estudio es su validez ecológica. Los resultados obtenidos y las sinergias que se desarrollan en los encuentros dialógicos multifamiliares aquí descritos nos permiten confiar en que otras maneras de hacer más alineadas con los principios de Diálogos Abiertos, con los recursos de que disponemos en nuestro contexto sanitario, son posibles ya (AU)

Introduction: We describe the experience of a multi-family group, directed at young people affected by their first psychotic crisis and their social networks, in a real clinical environment within the Spanish national health system, based on the Open Dialogue philosophy, in the context of the COVID-19 pandemic. Method: three families and three mental health professionals took part in the study. Instruments: SCORE-15, SWLS, CSQ-8 and a list of themes that appear in the dialogues.Results: both the five subjects and the facilitators perceive an improvement in the level of family functioning and the usefulness of the therapy; only one of the subjects reports an improvement in the level of life satisfaction at the end of the group; we observe high satisfaction on the part of the participants with the care received in the group. Discussion: the strength of this study is its ecological validity. The results obtained, and the synergies developed in the multifamily meetings described here, demonstrate that different methods more aligned with the principles of Open Dialogues are now possible with the resources available in our clinical context (AU)

Changes in Radical Levels as a Cause for the FLASH effect: Impact of beam structure parameters at ultra-high dose rates on oxygen depletion in water.

The influence of different average and bunch dose rates in electron beams on the FLASH effect was investigated. The present study measures O2 content in water at different beam pulse patterns and finds strong correlation with biological data, strengthening the hypothesis of radical-related mechanisms as a reason for the FLASH effect.

A structured approach to EHR surveillance of diagnostic error in acute care: an exploratory analysis of two institutionally-defined case cohorts.

OBJECTIVES: To test a structured electronic health record (EHR) case review process to identify diagnostic errors (DE) and diagnostic process failures (DPFs) in acute care. METHODS: We adapted validated tools (Safer Dx, Diagnostic Error Evaluation Research [DEER] Taxonomy) to assess the diagnostic process during the hospital encounter and categorized 13 postulated e-triggers. We created two test cohorts of all preventable cases (n=28) and an equal number of randomly sampled non-preventable cases (n=28) from 365 adult general medicine patients who expired and underwent our institution's mortality case review process. After excluding patients with a length of stay of more than one month, each case was reviewed by two blinded clinicians trained in our process and by an expert panel. Inter-rater reliability was assessed. We compared the frequency of DE contributing to death in both cohorts, as well as mean DPFs and e-triggers for DE positive and negative cases within each cohort. RESULTS: Twenty-seven (96.4%) preventable and 24 (85.7%) non-preventable cases underwent our review process. Inter-rater reliability was moderate between individual reviewers (Cohen's kappa 0.41) and substantial with the expert panel (Cohen's kappa 0.74). The frequency of DE contributing to death was significantly higher for the preventable compared to the non-preventable cohort (56% vs. 17%, OR 6.25 [1.68, 23.27], p<0.01). Mean DPFs and e-triggers were significantly and non-significantly higher for DE positive compared to DE negative cases in each cohort, respectively. CONCLUSIONS: We observed substantial agreement among final consensus and expert panel reviews using our structured EHR case review process. DEs contributing to death associated with DPFs were identified in institutionally designated preventable and non-preventable cases. While e-triggers may be useful for discriminating DE positive from DE negative cases, larger studies are required for validation. Our approach has potential to augment institutional mortality case review processes with respect to DE surveillance.

Human lung-cancer-cell radioresistance investigated through 2D network topology.

Radiation therapy (RT) is now considered to be a main component of cancer therapy, alongside surgery, chemotherapy and monoclonal antibody-based immunotherapy. In RT, cancer tissues are exposed to ionizing radiation causing the death of malignant cells and favoring cancer regression. However, the efficiency of RT may be hampered by cell-radioresistance (RR)-that is a feature of tumor cells of withstanding RT. To improve the RT performance, it is decisive developing methods that can help to quantify cell sensitivity to radiation. In acknowledgment of the fact that none of the existing methods to assess RR are based on cell graphs topology, in this work we have examined how 2D cell networks, within a single colony, from different human lung cancer lines (H460, A549 and Calu-1) behave in response to doses of ionizing radiation ranging from 0 to 8 Gy. We measured the structure of resulting cell-graphs using well-assessed networks-analysis metrics, such as the clustering coefficient (cc), the characteristic path length (cpl), and the small world coefficient (SW). Findings of the work illustrate that the clustering characteristics of cell-networks show a marked sensitivity to the dose and cell line. Higher-than-one values of SW coefficient, clue of a discontinuous and inhomogeneous cell spatial layout, are associated to elevated levels of radiation and to a lower radio-resistance of the treated cell line. Results of the work suggest that topology could be used as a quantitative parameter to assess the cell radio-resistance and measure the performance of cancer radiotherapy.

Preliminary Experience With the Human Acellular Vessel: A Descriptive Case Series Detailing Early Use of a Bioengineered Blood Vessel for Arterial Repair.

BACKGROUND: An infection-resistant, immediately available conduit for trauma and urgent vascular reconstruction remains a critical need for successful limb salvage. While autologous vein remains the gold standard, vein-limited patients and size mismatch are common issues. The Human Acellular Vessel (HAV) (Humacyte, Inc., Durham, NC) is a bioengineered conduit with off-the-shelf availability and resistance to infection, ideal characteristics for patients with challenging revascularization scenarios. This report describes HAV implantation in patients with complex limb-threatening ischemia and limited conduit options who may have otherwise faced limb loss. METHODS: The Food and Drug Administration (FDA) expanded-access program was used to allow urgent implantation of the HAV for arterial reconstruction. Electronic medical records were reviewed with extraction of relevant data including patient demographics, surgical implantation, patency, infectious complications, and mortality. RESULTS: The HAV was implanted in 8 patients requiring vascular reconstruction. Graft or soft tissue infection was present in 2 patients. One patient with severe penetrating pelvic injury had 4 HAV placed to repair bilateral external iliac artery and vein injuries. There was 1 technical failure due to poor outflow, 2 patients died unrelated to HAV use, and 5 lower extremity bypasses maintained patency at an average of 11.4 months (range: 4-20 months). No HAV infectious complications were identified. CONCLUSIONS: This report is the first United States series describing early outcomes using the HAV under the FDA expanded-access program for urgent vascular reconstruction. The HAV demonstrates resistance to infection, reliable patency, and offers surgeons an immediate option when confronted with complex revascularization scenarios. Assessment of long-term outcomes will be important for future studies.

Safety of Direct Oral Anticoagulants Compared to Warfarin for Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis.

The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation is limited and mostly founded on clinical trials that excluded this patient population. We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with post-operative cardiac surgery atrial fibrillation. We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality. We performed a random-effects meta-analysis of all outcomes. The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50-0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41-1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74-1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74-1.37, I2: 26.5%). Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding and mortality.

Introduction of a standardized protocol for cardiac risk assessment in candidates for liver transplant - A retrospective cohort analysis.

INTRODUCTION: Recommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed. METHODS: All patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018). We described clinical characteristics, candidacy for transplant, and cardiovascular complications during follow-up. As an unadjusted exploratory analysis, the Cochran-Armitage Exact Trend Test was used to examine univariate differences across time. RESULTS: A total of 462 patients underwent liver transplant evaluation during the study period. Among these, 218 (47.2%) patients underwent stress test, 50 (10.8%) underwent CCTA, and 68 (14.8%) underwent ICA. Across the three time periods, there was an increase in the proportion of CCTAs performed (3%, 6.3%, and 26.3% respectively; p <0.001) and proportion of patients diagnosed with obstructive CAD using CCTA (0%, 30%, and 51.4% respectively; p = 0.04). There was no significant difference in post-transplant cardiac complications among patients evaluated before 2018, during 2018, and after 2018 (5.9% vs. 5.6 vs. 6.0%; p=1.0). CONCLUSION: Our findings suggest it is reasonable to shift practice to a less invasive approach utilizing CCTA or nuclear stress testing when assessing liver transplant candidates at increased cardiovascular risk.

Colgajo sural superficial a pedículo distal excluyendo nervio sural: casuística / Superficial distally based sural flap with exclusion of the sural nerve: clinical cases

Introducción y objetivo: El colgajo fasciocutáneo sural superficial a pedículo distal ha sido utilizado desde hace tiempo para la reconstrucción del tercio distal de la pierna, tobillo y talón, y su irrigación también ha sido establecida.Presentamos nuestra casuística demostrando que este colgajo puede sobrevivir excluyendo de su composición el nervio sural y por lo tanto conservar la sensibilidad de tercio distal póstero-lateral de pierna y borde lateral del pié, conservando también su irrigación indemne.Material y método.Recogemos 40 pacientes con fractura expuesta de tercio distal de pierna, tobillo y talón, sometidos a reconstrucción con colgajo sural superficial a pedículo distal excluyendo el nervio sural, desde 1998 hasta 2019.Las edades fuctuaron entre 20 y 55 años; 35 hombres y 5 mujeres.En todos los pacientes realizamos prueba de presión cutánea suave con plumilla (pinch test ) y prueba del pinchazo cutáneo (pin prick), y en 4 neurografía sensorial.Resultados.La irrigación del colgajo no se vio alterada al excluir el nervio sural. Hubo 2 necrosis distales del colgajo solucionadas con injerto dermo-epidérmico y/o avance del colgajo. En 3 pacientes hubo edema resuelto con elevación de pierna y vendaje suave. En 4 pacientes hubo celulitis que cedió con antibióticos. La sensibilidad cutánea en el tercio distal de la pierna en su porción posterior y lateral, y en el borde lateral del pie se conservó sin alteraciones.Conclusiones.En nuestra casuística, la exclusión del nervio sural no alteró la irrigación del colgajo En nuestros pacientes, la sensibilidad cutánea del tercio distal de la cara póstero-lateral de la pierna y el borde lateral del pié no se alteró, siendo corroborada por la clínica y por la neurografía sensorial. (AU)

Background and objective: Background and objective. The distally based superficial sural artery flap has been used for lower limb reconstruction for long time. The blood supply for this flap has been studied for many authors.We present our casuistry showing that this flap can survive excluding the sural nerve from its composition and therefore preserve the sensitivity of the distal postero-lateral third of the leg and the lateral border of the foot, also preserving its undamaged irrigation.Methods.We have operated on 40 patients since 1998 to 2019, 35 men and 5 female, age ranged from 20 to 55 years old, using a superficial distally based sural flap, excluding the sural nerve. The pinch and the pin prick test were done in all patients.Results.In spite of excluding the sural nerve, the arterial blood supply to the flap was not compromised. There were 2 distal partial necrosis healed with flap advance and or split thickness skin graft. Edema was presented in 3 patients disappearing with limb elevation and light dressing. Cellulitis was presented in 4 patients and disappeared with antibiotics. Cutaneous sensitivity in the posterior and lateral distal third portion of the leg and in the edge of the foot was unalterable.Conclusions.In our clinical cases, the arterial blood supply to the distally based sural flap is not compromised with the exclusion of the sural nerve. The clinic and neurography show the patency of the sensation in the skin of the lateral and posterior part of the distal third of the leg and the lateral aspects of the foot.These findings allow to exclude the sural nerve from the flap insuring the blood supply and avoiding the possible pressure sores when the workers use their security shoes. (AU)

Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation.

Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, including cancer stem cells, remains the main challenge of radiotherapy. Recently, lipid droplets (LDs) have been proposed as functional markers of cancer stem cells, also being involved in increased cell tumorigenicity. LD biogenesis is a multistep process requiring various enzymes, including Diacylglycerol acyltransferase 2 (DGAT2). In this context, we evaluated the effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays. Our results demonstrated that 72 h of PF-06424439 treatment reduced LD content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. In addition, the combined treatment negatively interfered with lipid metabolism-related genes, as well as with EMT gene expression, and modulated the expression of typical markers associated with the CSC-like phenotype. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness.

Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance.

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma, and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of lipid droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect that might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

Analyzing diagnostic errors in the acute setting: a process-driven approach.

OBJECTIVES: We describe an approach for analyzing failures in diagnostic processes in a small, enriched cohort of general medicine patients who expired during hospitalization and experienced medical error. Our objective was to delineate a systematic strategy for identifying frequent and significant failures in the diagnostic process to inform strategies for preventing adverse events due to diagnostic error. METHODS: Two clinicians independently reviewed detailed records of purposively sampled cases identified from established institutional case review forums and assessed the likelihood of diagnostic error using the Safer Dx instrument. Each reviewer used the modified Diagnostic Error Evaluation and Research (DEER) taxonomy, revised for acute care (41 possible failure points across six process dimensions), to characterize the frequency of failure points (FPs) and significant FPs in the diagnostic process. RESULTS: Of 166 cases with medical error, 16 were sampled: 13 (81.3%) had one or more diagnostic error(s), and a total of 113 FPs and 30 significant FPs were identified. A majority of significant FPs (63.3%) occurred in "Diagnostic Information and Patient Follow-up" and "Patient and Provider Encounter and Initial Assessment" process dimensions. Fourteen (87.5%) cases had a significant FP in at least one of these dimensions. CONCLUSIONS: Failures in the diagnostic process occurred across multiple dimensions in our purposively sampled cohort. A systematic analytic approach incorporating the modified DEER taxonomy, revised for acute care, offered critical insights into key failures in the diagnostic process that could serve as potential targets for preventative interventions.

Caracterización clínico-epidemiológica de 77 niños y adolescentes infectados por el coronavirus SARS-CoV-2 / Clinical-epidemiological characterization of 77 children and adolescents infected with SARS-CoV-2 coronavirus

Introducción: Los niños también son susceptibles a la infección por SARS-CoV-2, pero sus manifestaciones clínicas son leves y la evolución en la mayoría de los casos es satisfactoria. Objetivo: Caracterizar clínica-epidemiológicamente a pacientes pediátricos infectados con el nuevo coronavirus SARS-CoV‐2. Métodos: Estudio descriptivo, transversal y retrospectivo en los primeros 77 pacientes menores de 18 años confirmados con COVID 19 e ingresados en las salas de pediatría del hospital "Dr. Luis Díaz Soto" en el período comprendido entre el 13 de marzo al 30 junio 2020. De las historias clínicas se tomaron los datos de las variables edad y sexo, comorbilidades, fuente de infección y lugar de exposición, presencia de síntomas y tiempo de aparición después del contacto y periodo en que se inició la mejoría. Resultados: Hubo discreto predominio del sexo femenino (54,5 por ciento) y los adolescentes (51,8 por ciento) más vulnerables a la infección. Se refirieron comorbilidades en 23 casos (22,8 por ciento) y el asma fue la más frecuente (10-13 por ciento). Se precisó la fuente de infección en 74 (96,1 por ciento) y 58 (75,3 por ciento) estaban asintomáticos al diagnóstico. Los síntomas más frecuentes fueron los respiratorios (tos 7-36,8 por ciento, rinorrea 5-26,3 por ciento y estornudos 4- 21,0 por ciento), le siguió la cefalea con 4 (21.0 por ciento); solo 3 presentaron fiebre (15,8 por ciento) y otros 3 anosmia-disgeusia (15,8 por ciento). La evolución fue favorable en 100,0 % de los pacientes y la mayoría estaba asintomática al 7mo. día. Conclusiones: La infección por SARS-CoV-2 se presentó sin distinción significativa de sexo, preferentemente en adolescentes, con manifestaciones leves de la enfermedad y evolución satisfactoria. No hubo fallecidos(AU)

Introduction: Children are also vulnerable to Sars-CoV-2 infections, but their clinical manifestations are slight and the evolution in most of the cases is satisfactory. Objective: Characterize in a clinical-epidemiological way pediatric patients infected with the new SARS-CoV-2 coronavirus. Methods: Descriptive, cross-sectional and retrospective study in the first 77 patients under 18 years confirmed with COVID-19 and admitted in the pediatric service of "Dr. Luis Díaz Soto" Hospital, in the period from March 13th to June 30th, 2020. From the clinical records were taken data of variables like age and sex, comorbidities, source of infection and place of exposure, presence of symptoms and time of onset after the contact, and period in which started an improvement of the disease. Results: There was a discreet predominance of female sex (54.5 percent) and the adolescents (51.8 percent) being more vulnerable to the infection. Comorbidities were noticed in 23 cases (22.8 percent) and asthma was the most frequent (10-13 percent). It was specified the source of infection in 74 patients (96.1 percent) and 58 patients (75.3 percent) were asymptomatic during the diagnosis. The most frequent symptoms were: respiratory ones (cough: 7-36.8 percent; rhinorrhoea: 5-26.3 percent; and sneezing: 4-21,0 percent); followed by cephalalgia with 4 (21,0 percent); just 3 patients presented fever (15.8 percent) and other 3 presented anosmia-dysgeusia (15.8 percent).The evolution was favorable in 100.0 percent of the patients and most of them were asymptomatic at the seventh day. Conclusions: The infection by SARS-CoV-2 was present with significative distinction of sex, more commonly in adolescents with slight manifestations of the disease and satisfactory evolution. There were no deaths(AU)

Modified T-Graft for Extracorporeal Membrane Oxygenation in a Patient with Small-Caliber Femoral Arteries.

Extracorporeal membrane oxygenation (ECMO) is generally used as a last resort to provide cardiopulmonary support in patients whose advanced cardiac or respiratory failure does not respond to less invasive treatments. Lower-limb ischemia secondary to the large diameter of the arterial cannula is one of ECMO's major limitations: in patients who have small-caliber arteries, the cannulas can reduce native blood flow. The creation of a T-graft-a well-described technique to avoid limb ischemia-enables flow into the ECMO cannula without jeopardizing blood flow to the limb. However, leaving the graft exposed through an open groin wound can result in dislodgment, and it increases the risk of infection. We describe our modification of a conventional T-graft in an 18-year-old woman who had systolic heart failure, acute respiratory distress syndrome, and small-caliber femoral vessels. We tunneled a polytetrafluoroethylene graft inside a Dacron graft, then ran the combined graft through a subcutaneous tunnel similar to that created for a peripheral bypass. Thus, the graft was protected from environmental exposure and the risk of infection. Our technique seems safer and more secure than the original T-graft technique, and we recommend its consideration during ECMO cannulation.